No effect of acute tryptophan depletion on phosphodiesterase inhibition-related improvements of short-term object memory in male Wistar rats

E.L. van Donkelaar, J. Prickaerts, S. Akkerman, K. Rutten, Harry Steinbusch, A. Blokland

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

ObjectiveTo further explore the implication of the serotonin (5-HT) system in the improvement of rat short-term object recognition after administration of the type 2 phosphodiesterase inhibitor (PDE-I) BAY 60-7550 and the type 5 PDE-I vardenafil, the effect of PDE2 and PDE5 inhibition upon central amino acid levels, 5-HT, and related parameters were measured after applying acute tryptophan depletion (ATD). MethodWistar rats were orally administered saline or a protein-carbohydrate mixture with or without tryptophan (TRP). TRP-depleted animals additionally received an oral vehicle injection or the PDE inhibitors BAY 60-7550 or vardenafil at a dose known to improve object memory performance. ResultsAlthough ATD significantly decreased TRP levels in the hippocampus 2h after administration, 5-HT levels appeared only moderately affected, without any changes observed in the amount of 5-HIAA or 5-HT turnover rate. Moreover, no effects of PDE inhibition upon 5-HT or related parameters were observed. ConclusionChanges in 5-HT neurotransmitter activity might be excluded as a potential underlying mechanism of the previously reported ability of PDE inhibitors to improve short-term object memory in rats. It is suggested that a decrease in cerebral blood flow potentially underlies ATD-induced object memory deficits, most likely due to decrease in NO synthesis.
Original languageEnglish
Pages (from-to)107-113
Number of pages7
JournalActa Psychiatrica Scandinavica
Volume128
Issue number2
DOIs
Publication statusPublished - Aug 2013

Keywords

  • phosphodiesterase inhibitors
  • acute tryptophan depletion
  • serotonin
  • rat object memory
  • CEREBRAL-BLOOD-FLOW
  • GELATIN-BASED MIXTURE
  • NITRIC-OXIDE SYNTHASE
  • AFFECTIVE BEHAVIOR
  • SEROTONIN RELEASE
  • AMINO-ACIDS
  • BRAIN
  • DOPAMINE
  • CGMP
  • NORADRENALINE

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